The present studies are designed to investigate the various possible sites of interaction between the two hormones primarily responsible for the control of mammalian calcium homeostasis, PTH and vitamin D. A systematic investigation of the effects of various vitamin D metabolites (25(OH)D3, 1,25(OH)2D3 and 24,25(OH)2D3) on PTH secretion is proposed. Detailed studies of the mechanism(s) of action of vitamin D on PTH secretion are planned. Other non-ionic factors (e.g, gastrointestinal hormones) which may affect PTH secretion will be studied. The value of 24,25(OH) as a possible therapeutic agent for hyperparathyroid states will be studied first in animals and then in man. The role of vitamin D in PTH metabolism will be studied by a series of in vivo and in vitro experiments. Miscellaneous clinical studies will include assessment of the immunoassay procedure in pre-operative localization of abnormally functioning parathyroid glands, investigations into the mechanisms of the hypercalcemia of immobilization and studies concerning the role of PTH or PTH-like materials in certain hypercalcemias associated with malignancy.